Towards the development of an immuno MALDI (iMALDI) mass spectrometry assay for the diagnosis of hypertension
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- 作者：Jennifer D. Reid (1) (2)
Daniel T. Holmes (3)
D. Randal Mason (1) (2)
Brinda Shah (1) (2)
Christoph H. Borchers (1) - 刊名：Journal of The American Society for Mass Spectrometry
- 出版年：2010
- 出版时间：October 2010
- 年：2010
- 卷：21
- 期：10
- 页码：1680-1686
- 全文大小：510KB
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Daniel T. Holmes (3)
D. Randal Mason (1) (2)
Brinda Shah (1) (2)
Christoph H. Borchers (1)
1. University of Victoria-Genome British Columbia Proteomics Centre, University of Victoria, Victoria, British Columbia, Canada
2. Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada
3. Department of Pathology and Laboratory Medicine, University of British Columbia, St. Paul鈥檚 Hospital, Vancouver, British Columbia, Canada
文摘
The renin-angiotensin-aldosterone system (RAAS) plays an essential role in the regulation of plasma volume and arterial blood pressure. One of the most common diseases of the RAAS is the autonomous production of aldosterone by the adrenal glands, caused by either bilateral adrenal hyperplasia or an aldosterone-producing adenoma. This condition, known as primary aldosteronism, is a treatable and often curable form of hypertension. The measurement of plasma renin activity (PRA), as determined by radioimmunoassay for angiotensin I is essential to the diagnosis of primary aldosteronism. However, accurate determination of PRA is often hampered by low plasma concentrations of angiotensin I. Here, we report the use of immuno-MALDI (iMALDI) as a highly sensitive and specific method for the absolute quantitation of angiotensin I in plasma. iMALDI permits concentration determination by affinity-capture of angiotensin I and a stable-isotopically labeled standard (SIS) peptide on immobilized anti-peptide antibodies. The affinity beads are placed on the MALDI target, permitting automated analysis of large numbers of patient samples. Pretreatment of the plasma is not required, and this method is suitable for the accurate determination of angiotensin I in whole plasma. The calibration curve generated using this method was linear over a 50-fold concentration range in plasma, with a correlation coefficient of 0.984. MS/MS sequence confirmation provides absolute specificity. The iMALDI angiotensin I assay, therefore, has the potential to be developed into a method for determining PRA that has advantages in time, in specificity, and in safety.